胆碱受体阻断剂优质PPT课件.ppt

单击此处编辑母版标题样式,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,胆碱受体阻断剂,Cholinoceptor blocking drugs,Cholinoceptor blocking drugs,:,Bind to cholinoceptor(affinity),but can not or has little result in cholinomimetic action(intrinsic activity),preventing the binding the receptor site to the cholinergic transmitter or cholinoceptor agonist,，,therefore result in anticholinic effects.,On the basis of specific receptor affinities(receptor selectivity of these antagonists),the antagonist fall into two major families.,Cholinoceptor blocking drugs,classify,drugs,Antimuscarinic agents,M,1,、,M,2,R antagonists,atropine scopolamine anisodamine,M,1,R antagonists,pirenzepine,M,2,R antagonists,gallamine,Antinicotinic agents,N,1,R antagonists,mecamylamine,N,2,R antagonists,succinylcholine tubocurarine,Antimuscarinic agents,plant,alkaloids,Atropa belladonna,Hyoscyamine(atropine),Datura stramonium,Hyoscyamine,Datura sp.,Feng qieer,scopolamine,Hyoscyamus niger,tianxianzi,Hyoscyamine,Scopolia tangutica,AT,3,anisodamine,Antimuscarinic agents,Atropa belladonna,颠茄,Atropine,阿托品,dl-hyoscyamine,Scopolamine,东莨菪碱,Anisodamine,山莨菪碱,654 654-2,AT,3,樟柳碱,Antimuscarinic agentsatropine,阿托品,1.,pharmocokinetics,tertiary amine alkaloid esters,Absorption:,well,absobed from the gut and across the conjunctival membrane.Oral administration t,max,1h,；,injection t,max,15-20 min.,Distribution:,widely,，,passing across blood-brain barrier,Antimuscarinic agentsatropine,阿托品,Metabolism and excretion,:,disappear rapidly from the blood,half-life,of 2-2.5 hours,1/3 of the dose is excreted unchanged in the urine,most of the rest(2/3)appears in the urine as hydrolysis and conjugation products.,The effect of the drug on parasympathetic function decline rapidly in all organs except the eye.Effects on the iris and ciliary muscle persist for 72 hours or longer.,Antimuscarinic agentsatropine,阿托品,2.,pharmacodynamics and clinical uses,Mechanism of action,competitively block muscarinic receptors(atropine and Ach or cholinomimetics competition for a common binding site on the receptor protein),highly selective for muscarinic receptor,its potency at nicotinic receptors is much lower than at MR,large dose it has ganglion-blocking action.,Antimuscarinic agentsatropine,阿托品,The effectiveness varies with the tissue and atropine effects are dose dependent,the action appears in order as follow duo to increase of dose,：,glands secretions decrease,mydriasis,bradycardia,smooth muscle relax,tachycardia,gastric secretion depress,CNS signs.,Antimuscarinic agentsatropine,阿托品,1,reduction of gland secretion,salivary gland,sweat glands:greatly reduced(small dose 0.5mg),dry mouth,dry skin(or red skin),lacrimal glands,bronchial glands:decreased(large dose),dry or sandy eyes,reduction the accumulation of secretions in the trachea.,gastric secretion,，,gastric acid(more large dose),thermoregulatory sweating suppressed and body temperature is elevated(large doses or infants and children):,may cause atropine fever,Antimuscarinic agentsatropine,阿托品,Clinical pharmacology(therapeutic applications),salivate,night sweat,(hyperhidrosis),preanesthetic treatment,(used prior to administration of inhalant anesthetics to depress bronchial secretion and to reduce the possibility of laryngospasm,to prevent pronounced bradycardia during abdominal surgical procedures),Antimuscarinic agentsatropine,阿托品,2,ophthalmologic disorders,mydriasis,cycloplegia,blocked of the ciliary muscle,loss of the ability to accommodate,cannot focus for near vision,increase,intraocular pressure,narrow anterior chamber angle,Antimuscarinic agentsatropine,阿托品,application,：,1),prevent synechia(adhesion)formation in uveitis and iritis,2),ophthalmoscopic examination:because it is a long-acting drug(duration of effects are 7-10 days),so shorter-acting drugs are preferred(homatromine),3),optometry,always measurement in young children,Antimuscarinic agentsatropine,阿托品,Antimuscarinic agentsatropine,阿托品,3,cadiovascular systerm,1)heart,0.5mg bradycardia brevity,and not marked,(initial)(central),1-2mg tachycardia(blockade of vagal),toxic concentration intraventricular conduction block,Antimuscarinic agentsatropine,阿托品,2),the effects on blood vessels and blood pressure,treatment dosage (no direct innervation from the parasympathetic nervous systerm)no effects on BP,larger dose vasodilation(cutaneous,especially in the upper portion of the body),Application:infectious shock,bradycardia and A-V block,Antimuscarinic agentsatropine,阿托品,4,smooth muscles:relaxation,characteristic,1)selectivity,gastrointestinal smooth musclebladder detrusorbile duct and ureteruterus,bronchial muscle;no effect on sphincter,2)atropine abolishes any excessive tone and mobility of the intestinal tract,but it has relatively little effect on normal motility.,atropine,阿托品,4,smooth muscle:relaxation,application,：,gastrointestinal disorder(spasm,bellyache etc),reduce involuntary voiding in patients(urinary incontinence),eg children with meninggomyelocele,urinary urgency(inflammatory bladder disorder),gallbladder angina,（,adding pethidine),Antimuscarinic agentsatropine,阿托品,5,CNS:,Therapeutic dose:no significant effect,Then high dose:minimal,stimulant,effects on the central nervous system,especially the parasympathetic medullary centers,(respiration center,excitement,agitation,hallucinations),severity inhibition(coma),Antimuscarinic agentsatropine,阿托品,6,Therapeutic applications,：,cholinergic poisoning,Treatment of poisoning of organophosphates or some mushroom,rapidly combat the muscarinic effects,reverse some central nervous system effects,large dose blockade N,1,receptor,principle of application,：,forepart,large doses(enough dose),repeat(continuance),administration,Antimuscarinic agentsatropine,阿托品,atropine change,阿托品化,Reversal of miosis(mydriasis),dry mouth,face flushed,dry skin,mild restlessness,rapid pulse(100-120/min,）,pulmonary rale obviously reduce or disappear,atropine,阿托品,adverse reaction,*,broad range of antimuscarinic effects,treatment with atropine directed at one organ system almost always induces undesirable effects in the other organ system,signs:dry mouth,mydriasis,blurred vision,photophobia,face flushed,hot and flushed skin,slight restlessness,tachycardia,agitation,delirium,high temperature,dysuria etc,*,The antidote of atropine poisoning:pilocarpine,neostigimine,contraindications,glaucoma prostate hyperplasia(hypertrophy),Antimuscarinic agents,atropine,654-2,scopolamine,AT,3,Smooth muscle,relax,weak,similar,weak,glands,secrete,weak,potent,weak,eye,mydriasis,weak,potent,weak,Cardiovascular S,tachycardia,similar,weak,weak,CNS,excite,similar,Sedation hypnosis,Sedation hypnosis,LD,50,mg/kg,98,115,155,506,Antimuscarinic agents,atropine,654-2,anisodamine,scopolamine,AT,3,application,gastrointestinal spasm,Ophthalmologic disorders,arrhythmia,infection shock,organophosphates poisoning,preanesthetic treatment,gastrointestinal,spasm,infection shock,organophosphates,poisoning,preanesthetic treatment,Motion sickness,parkinsonism,Headache,acute paralysis,induced by brain blood vessels,Antimuscarinic agents,Substitute of atropine,Ophthalmic refraction homatropine,tropicamide,Spasmolytic agents propantheline,glycopyrrolate oxybutynin,Gastric ulcer,duodenum peptic ulcer,pirenzepine,telenzepine,Antinicotinic agents,N,1,R antagonists,ganglion-blocking drugs,N,2,R antagonists,skeletal muscle relaxants,The muscle-relaxant drugs most commonly used act by interrupting transmission at the junction between somatic motor nerves and skeletal muscle fibers(interfere with transmission at the neuromuscular end plate),prevent access of the transmitter to its receptor and prevent muscle contraction.,Antinicotinic agents,The two classes of neuromuscular blocking drugs block this process by different mechanisms：,nondepolarizing drugs(competitive antagonists)compete with Ach in binding to the receptor site.,depolarizing drugs maintain end plate membrane depolarization and thus prevent transmission of another action potential.,Antinicotinic agents,depolarizing drugs,transient muscle fasciculation,occur(initial excitatory effect on skeletal muscle,especially over the chest and abdomen),easy to produce resistance（continued exposure to succinylcholine）,cholinesterase inhibitor augment not reverse,Suxamethonium,（,succinylcholine,scoline,琥珀胆碱,）,onset of neuromuscular blocked is very rapid(within 1min),short duration of action,application:trachea intubatton,celioscope examination,adjuncts to anesthesia,Antinicotinic agents,nondepolarizing drugs,act predominantly at the nicotinic receptor site to compete with Ach.,AchE inhibitors(eg,neostigimine)to antagonize nondepolarizing drugs,d-tubocurarine,（筒箭毒碱）,atracurium,(isoquinoline derivatives and steroids),Quaternary nitrogens(poorly lipid soluble),primaryily as adjuncts to general anesthesia,